Congenital Diaphragmatic Hernia (CDH) is a common birth defect that is associated with a significant mortality rate. CDH newborns die largely because of insufficient lung function. Those that do survive are more susceptible to developing asthma and pulmonary hypertension. A popular view of the cause of CDH is that it arises from diaphragm malformations, which then allows abdominal organs into the chest, compressing the lung. We present data from mouse genetic models of CDH that demonstrate diaphragm-independent origins of disease. We propose to use these models to uncover the primary cause, trace disease progression, and identify novel nodes of the pathogenesis process where informed clinical interventions would increase survival and decrease morbidities.